The demand for optically active compounds has grown rapidly in recent years, and particularly demand for pharmaceutical intermediates in the pharmaceutical industry is increasing. Accordingly, a method of obtaining optically active compounds efficiently is intensively studied. One method of obtaining optically active compounds is an optical resolution method. Preferential crystallization, diastereomer resolution, kinetic resolution and the like are known as the optical resolution methods. Since the preferential crystallization has a narrow scope of application, obtainable compounds are remarkably limited. The diastereomer resolution requires a stoichiometric resolving agent and multi stages, and its operation is troublesome. On the other hand, the kinetic resolution method is a technique for performing optical resolution characterized by utilizing differences in reaction rate between racemates and enantiomers caused by performing reactions using optically active catalysts, thereby reacting only a specific enantiomer preferentially. The kinetic resolution using enzymes mainly comes in practice and is an effective method for obtaining optically active amino acids, alcohols and the like. However, since the kinetic resolution with enzymes generally requires long time for the reactions, and concentrations of substrates must be diluted in order to obtain high optical yields, this method is unsuitable for obtaining large amounts of optically active compounds.
Some studies of kinetic optical resolution by chemical techniques have been reported. For example, as a chemical method of optically resolving carboxylic acid derivatives such as amino acids, an optical resolution by alcoholysis of urethane-protected amino acid-N-carboxy anhydrides (UNCA) using cinchona alkaloid derivatives as catalysts was reported recently (Deng, L. et al. J. Am. Chem. Soc., 2001, 123, 12696-12697). This report states that quinidine, which is cinchona alkaloid, is effective as a catalyst in these reactions, and use of (DHQD)2AQN and DHQD-PHN, which are quinidine derivatives having alcohol moiety protected with an aryl group, leads to more efficient optical resolution. However, since (DHQD)2AQN and DHQD-PHN are difficult to synthesize, very expensive and hardly available, they are unsuitable for optical resolution in large amounts. It is necessary to use quinidine, which is readily available and inexpensive, in order to perform optical resolution in large amounts, but use of quinidine causes issues in recycling of the catalyst, namely, quinidine itself is reacted with UNCA to give by-products, which lowers purity of the recovered catalyst. Using (DHQD)2AQN and quinidine as catalysts, optical resolution in high substrate concentrations causes the problem that enantiomer selectivity is lowered. Accordingly, development of new catalysts which are readily available and stable and have high optical resolution ability is desired.